The overall goal of this U54 application is to support a highly multidisciplinary team of expert chemists, engineers, biologists, material scientists and clinicians to develop and rapidly translate new nanotechnologies to better diagnose and treat cancer in the clinic. This team formed a Center for Cancer Nanotechnology Excellence (CCNE) in 2004 and over the past 5 years has shown extraordinary productivity through its integrated research programs and shared resources. The primary team includes investigators from Massachusetts Institute of Technology (MIT), Harvard Medical School (HMS), Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH) and Harvard Faculty of Arts and Sciences (FAS). The CCNE thus effectively bridges programs in basic sciences at two Universities (MIT and Harvard) and clinical programs at leading Hospitals (MGH and BWH). The program will continue to be headed up by Dr. Robert Langer and Dr. Ralph Weissleder as Co-Pls. Dr. Langer is Institute Professor at MIT and member of the Koch Institute for Integrative Cancer Research at MIT (Kl). Dr. Weissleder is a Professor at Harvard Medical School, the Director of the Center for Systems Biology at MGH, a practicing clinician at MGH and a member of the Dana Farber Harvard Cancer Center. Public Health Relevance: With recent advances in nanotechnology and the introduction of some new nanomaterials into clinical trials, a myriad of opportunities are available to advance medical science and disease treatment. The translational goal is now to better control and manipulate emerging new materials by precisely configuring molecular structures, adding biological functionalities, decreasing or eliminating toxicities, and creating supramolecular